Related Experiment Video

Updated: Jun 7, 2025

Phosphorus-31 Magnetic Resonance Spectroscopy: A Tool for Measuring In Vivo Mitochondrial Oxidative Phosphorylation Capacity in Human Skeletal Muscle
09:40

Phosphorus-31 Magnetic Resonance Spectroscopy: A Tool for Measuring In Vivo Mitochondrial Oxidative Phosphorylation Capacity in Human Skeletal Muscle

Published on: January 19, 2017

11.7K

Mitochondrial bioenergetics deficiency in cisd-1 mutants is linked to AMPK-mediated lipid metabolism

Kuei-Ching Hsiung1, Hsiang-Yu Tang2, Mei-Ling Cheng3

  • 1Department and Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.

Biomedical Journal
|November 9, 2024
PubMed
Abstract

Insights

Mitochondrial protein CISD-1 deficiency lowers ATP levels. Worms activate AMP-activated protein kinase (AMPK) to boost energy production through lipid breakdown, maintaining cellular function.

Area of Science:

  • Mitochondrial Bioenergetics
  • Cellular Metabolism
  • Molecular Biology

Background:

  • CISD-1, a mitochondrial iron-sulfur protein, is implicated in diseases like cancer and diabetes.
  • Previous studies showed CISD-1 deficiency in worms reduces glucose and ATP levels.
  • This study investigates compensatory mechanisms in worms experiencing lower ATP levels.

Purpose of the Study:

  • To explore how worms compensate for reduced ATP levels caused by CISD-1 deficiency.
  • To analyze changes in iron content, AMPK activity, and lipid profiles.
  • To elucidate the signaling pathway linking ATP deficiency to energy compensation.

Main Methods:

  • Western blot and fluorescence microscopy to assess CISD-1 expression and protein localization.
  • Analysis of total and mitochondrial iron content, electron transport chain complexes, and AMPK activity.
  • RT-qPCR for mitochondrial beta-oxidation gene expression and lipidomic analysis.

Main Results:

  • CISD-1 defects disrupt iron transport, causing proton leak and reduced ATP production via the electron transport chain.
  • ATP deficiency activates AMP-activated protein kinase (AMPK).
  • Activated AMPK upregulates genes for lipolysis through beta-oxidation, facilitating compensatory energy production.

Conclusions:

  • A functional link exists between CISD-1 and AMPK in regulating mitochondrial energy homeostasis.
  • This coordination acts as a quality control mechanism for mitochondrial bioenergetics.
  • The pathway provides compensatory energy resources to mitigate ATP deficiency.
Keywords:
AMPKC. elegansIron-sulfate containing proteinLipid droplet sizeLipidomicMitochondria outer membrane protein

More Related Videos

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess07:35

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess

Published on: June 1, 2022

2.2K
Visualization of Mitochondrial Respiratory Function using Cytochrome C Oxidase / Succinate Dehydrogenase COX/SDH Double-labeling Histochemistry06:53

Visualization of Mitochondrial Respiratory Function using Cytochrome C Oxidase / Succinate Dehydrogenase COX/SDH Double-labeling Histochemistry

Published on: November 23, 2011

36.7K

Related Concept Videos

Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
11.9K
Amino Acid Catabolism01:18

Amino Acid Catabolism

Microorganisms rely on proteins as an essential carbon and energy source, particularly in environments with limited polysaccharides or lipids. However, proteins are too large to cross the plasma membrane unaided, necessitating enzymatic degradation. Microbes secrete extracellular proteases and peptidases that hydrolyze proteins into peptides, which can then be transported across the membrane. Once inside the cell, intracellular proteases degrade these peptides into free amino acids, which...
1
ATP Synthase: Mechanism01:48

ATP Synthase: Mechanism

In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
13.9K
The Inner Mitochondrial Membrane01:28

The Inner Mitochondrial Membrane

The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria.  In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
3.3K
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.0K